Journal Articles
Amir Garakani, Frank D Buono, Mona Salehi, Melissa C Funaro, Anna Klimowicz, Harshit Sharma, Clara G F Faria, Kaitlyn Larkin and Rafael C Freire.
Acta Psychiatr Scand. 2024 Apr;149(4):295-312.
PMID: 38382649
DOI: 10.1111/acps.13669
Abstract
Background: Although not approved for the treatment of anxiety disorders (except trifluoperazine) there is ongoing off-label, unapproved use of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) for anxiety disorders. There have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of which focused on SGAs.
Objective: The specific aims of this umbrella review are to: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to traditional antidepressant treatments and other nonantipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects. The review protocol is registered on PROSPERO (CRD42021237436).
Methods: An initial search was undertaken to identify systematic reviews and meta-analyses from inception until 2020, with an updated search completed August 2021 and January 2023. The searches were conducted in PubMed, MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), and the Cochrane Library through hand searches of references of included articles. Review quality was measured using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) scale.
Results: The original and updated searches yielded 1796 and 3744 articles respectively, of which 45 were eligible. After final review, 25 systematic reviews and meta-analyses were included in the analysis. Most of the systematic reviews and meta-analyses were deemed low-quality through AMSTAR-2 with only one review being deemed high-quality. In evaluating the monotherapies with antipsychotics compared with first-line treatments for anxiety disorder there was insufficient evidence due to flawed study designs (such as problems with randomization) and small sample sizes within studies. There was limited evidence suggesting efficacy of antipsychotic agents in anxiety disorders other than quetiapine in generalized anxiety disorder (GAD).
Conclusions: This umbrella review indicates a lack of high-quality studies of antipsychotics in anxiety disorders outside of the use of quetiapine in GAD. Although potentially effective for anxiety disorders, FGAs and SGAs may have risks and side effects that outweigh their efficacy, although there were limited data. Further long-term and larger-scale studies of antipsychotics in anxiety disorders are needed.
Keywords: atypical antipsychotic; panic disorder; phobia; social anxiety disorder; typical antipsychotic.
Tamadhir Al-Mahrouqi, Mohammed Al Alawi and Rafael C Freire.
Clin Pract Epidemiol Ment Health, 2023. Aug 30:19:e174501792307240.
PMID: 37357687
DOI: 10.2174/17450179-v19-230823-2023-4
Abstract
Depressive disorders (DD) are common, and their prevalence is expected to rise over the next decade. Depressive disorders are linked to significant morbidity and mortality. The clinical conundrum of depressive disorders lies in the heterogeneity of their phenomenology and etiology. Further, the currently available antidepressants have several limitations, including a delayed onset of action, limited efficacy, and an unfavorable side effect profile. In this review, Dexmedetomidine (DEX), a highly selective and potent α2-adrenergic receptor (α2-AR) agonist, is proposed as a potentially novel antidepressant with multiple mechanisms of action targeting various depression pathophysiological processes. These mechanisms include modulation of the noradrenergic system, regulation of neuroinflammation and oxidative stress, influence on the Brain-Derived Neurotrophic Factor (BDNF) levels, and modulation of neurotransmitter systems, such as glutamate. The review begins with an introduction before moving on to a discussion of DEX’s pharmacological features. The pathophysiological and phenomenological targets of DD are also explored, along with the review of the existing preclinical and clinical evidence for DEX’s putative anti-depressant effects. Finally, the review ends by presenting the pertinent conclusions and future directions.
Keywords: Adrenergic alpha-agonists; Antidepressant; Depression; Dexmedetomidine; Major depressive disorder; Treatment resistant-depression.Accordion Content
Rafael C R Freire and Antonio E Nardi.
Expert Rev Neurother. 2023 Jul-Dec;23(8):677-679.
PMID: 37357687
DOI: 10.1080/14737175.2023.2229955
No abstract available
Keywords: Recurrence; agoraphobia; benzodiazepine; cognitive behavioral therapy; selective serotonin reuptake inhibitor; serotonin and noradrenaline reuptake inhibitor; tricyclic antidepressant.
Clara Gitahy Falcão Faria, Ursula Medeiros Araujo de Matos, Liana Llado-Medina, Victor Pereira-Sanchez, Rafael Freire and Antonio Egidio Nardi.
Front Psychiatry. 2022 Sep 13:13:910410.
PMID: 36177216.
DOI: 10.3389/fpsyt.2022.910410
Abstract
Despite the speedy development of vaccines for COVID-19, their rollout has posed a major public health challenge, as vaccine hesitancy (VH) and refusal are high. Addressing vaccine hesitancy is a multifactorial and context-dependent challenge. This perspective focuses on VH in the world region of Latin America and the Caribbean (LAC) and includes people suffering from severe mental illness, therefore covering populations and subpopulations often neglected in scientific literature. We present an overview of VH in LAC countries, discussing its global and historical context. Vaccine uptake has shown to widely vary across different subregions of LAC. Current data points to a possible correlation between societal polarization and vaccination, especially in countries going through political crises such as Brazil, Colombia, and Venezuela. Poor accessibility remains an additional important factor decreasing vaccination rollout in LAC countries and even further, in the whole Global South. Regarding patients with severe mental illness in LAC, and worldwide, it is paramount to include them in priority groups for immunization and monitor their vaccination coverage through public health indicators.
Keywords: COVID-19; Latin America and the Caribbean; mental health; severe mental illness; vaccine hesitancy.
Anxiety disorders, including panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), agoraphobia, and specific phobia, are among the most common psychiatric disorders. Although the traditional pharmacologic treatments for anxiety included barbiturates and then benzodiazepines, the introduction of tricyclic antidepressants, followed by the selective serotonin reuptake inhibitors (SSRIs), marked a tidal shift in the treatment of anxiety. Although not approved for treatment of anxiety disorders (with the exception of trifluoperazine) there is ongoing off-label, unapproved use of both first-generation “typical” antipsychotics (FGAs) and second-generation or “atypical” antipsychotics (SGAs) for anxiety. Although there have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of these reviews focused on SGAs, primarily the use of quetiapine in GAD. Given that there is little known about the potential benefits and short-and long-term risks of using antipsychotics in anxiety, there is a need for an umbrella review of systematic reviews and meta-analyses of the use of both FGAs and SGAs in anxiety disorders. The specific aims of this study are as follows: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs) and other non-antipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects; and (3) Evaluate the short- and long-term risks and side effects of prescribing antipsychotics in anxiety disorders. The review is registered on PROSPERO (CRD42021237436). Since data extraction has not begun, there is not preliminary data to share.
Increased CO2 sensitivity is common in panic disorder (PD) patients. Free divers who are known for their exceptional breathing control have lower CO2 sensitivity due to training effects. This study aimed to investigate the immediate effects of cold facial immersion (CFI), breath holding and CO2 challenges on panic symptoms. Healthy participants and patients with PD were subjected to four experimental conditions in a randomly assigned order. The four conditions were (a) breath-holding (BH), (b) CFI for 30 s, (c) CO2 challenge, and (d) CO2 challenge followed by CFI. Participants completed a battery of psychological measures, and physiological data (heart rate and respiration rate) were collected following each experimental condition. Participants with PD were unable to hold their breath for as long as normal controls; however, this finding was not significant, potentially due to a small sample size. Significant reductions in both physiological and cognitive symptoms of panic were noted in the clinical group following the CFI task. As hypothesized, the CFI task exerted demonstrable anxiolytic effects in the clinical group in this study by reducing heart rate significantly and lessening self-reported symptoms of anxiety and panic. This outcome demonstrates the promise of the CFI task for clinical applications.
Background: Mindfulness-based interventions (MBIs) are effective for some, but not all patients with anxiety disorders, but no clinical features have been consistently able to differentiate which patients are more likely to respond. In this study, we tested heart rate variability (HRV), a proposed correlate of regulated emotional response, as a moderator of treatment response to an MBI compared with pharmacotherapy.
Methods: Seventy-seven patients with GAD had HRV data collected before randomization to pharmacological treatment with fluoxetine or Body-in-Mind Training (an MBI focused on bodily movement attention). HRV was used to predict treatment response measured by the Hamilton anxiety rating scale at 0 (baseline), 5, and 8 weeks (end of the intervention).
Results: The HF (nu) index of HRV was a strong moderator of treatment response between BMT and fluoxetine (estimate = 4.27 95%CI [1.19, 8.19]). Although fluoxetine was overall slightly superior to BMT in this study, no differences were found between groups in patients with high HF (nu) scores (estimate = -1.85 CI95% [-9.21, 5.52]). In contrast, patients with low HF (nu) achieved lower anxiety rating scores with fluoxetine treatment when compared with BMT (estimate = -10.29, 95% CI [-17.59, -2.99]).
Limitations: A relatively small sample of patients was included.
Conclusions: HRV was able to identify a subgroup for which MBI was less effective than pharmacotherapy and is a promising candidate as a selective biomarker for treatment response between an MBI and fluoxetine.
The purpose of this Research Topic was to collect original papers and review articles exploring promising novel medications on the pipeline for anxiety disorders, primarily GAD, PD, SAD and SP, after first reviewing the current state of psychopharmacological treatments available. The topic aimed to explore more unique pathways for targeting treatment response in anxiety disorders, including the glutamate system, neurosteroids, the hypothalamic-pituitary-adrenal (HPA axis), neuropeptides, cannabinoids, and phytochemicals.
Aims:
To ascertain if virtual reality exposure therapy (VRET) is an effective add-on tool in the treatment of Panic Disorder (PD).
Background:
The exposure to virtual stimuli has been studied as a useful treatment for PD. However, the studies with PD are still scarce and use dissimilar protocols, with effectiveness varying according to the protocol applied.
Method:
Eight PD patients received VRET as an add-on treatment to pharmacotherapy. The treatment protocol consisted of eight sessions. The first session is for the patient to understand the treatment and to answer the questionnaires. The second and third sessions were to prepare the patients for exposures with breathing training using diaphragmatic breathing and others breathing techniques to manage anxiety. From the fourth to eighth sessions, the patients followed a hierarchy of tasks during virtual reality exposure. Clinicians rated the Clinical Global Impression Scale (CGI) and the Panic Disorder Severity Scale (PDSS). The patients rated the Diagnostic Symptom Questionnaire (DSQ); the Mobility Inventory (MI), the Anxiety Sensibility Index (ASI-R), the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI) and the WHOQOL-BREF before and after the protocol. After all exposures, the Igroup Presence Questionnaire (IPQ) was applied to measure the sense of presence experienced in the virtual environment. The virtual environment simulated the subway of Rio de Janeiro.
Result:
There were no statistically significant improvements in the CGI-S, PDSS, BAI, MI or WHOQOL. There was a significant improvement in the BDI scores (P = 0.033). There was a trend towards improvement of anxiety measured by the ASI-R (P = 0.084) and of panic symptoms measured by the DSQ (P = 0.081) scores. There was also a significant improvement of sense of presence (IPQ – general presence) through the exposure sessions.
Conclusion:
Our study demonstrated that VRET as an add-on to pharmacological therapy could benefit PD patients. Despite the lack of significant differences in the means, the dispersion of PDSS and BAI scores were smaller after treatment compared to before treatment, suggesting that patients with more severe anxiety, panic and agoraphobia symptoms benefited more of the VRET protocol so, at the end of the treatment, differences were found in important measures of panic. Randomized controlled clinical trials are warranted to confirm the efficacy of VRET.
There is currently much discussion about the similarities and differences between behavioral addictions and substance addictions. Recent studies indicate that the core elements of substance addictions, including tolerance, inability to reduce the use/behavior, continued use/behavior despite negative consequences and withdrawal are also present in behavioral addictions. In recent years there has been an exponential growth in the prevalence of behavioral addictions, which is driven by internet-related behavioral addictions. The prevalence of these addictions can be as high as 38% in young people, but it is probably lower in older adults.1 Internet gaming disorder (IGD) is the most studied internet-related behavioral addiction and probably the most severe. Among internet-related behavioral addictions, IGD was the only one included in DSM5, being described as a condition that requires additional research to be included in the main part of the manual. However, abundant evidence in the literature indicates that excessive use of social networking sites and messaging services also produces a negative impact on affected subjects.
Objective: Treatment for major depressive disorder (MDD) have evolved, although there is still a strong unmet need for more effective and tolerable options. The present study summarizes and discusses recent evidence regarding the non-transcranial magnetic stimulation (non-TMS) neurostimulation treatment for MDD.
Methods: The authors reviewed non-TMS neurostimulation clinical trials for MDD between 2010 and 2020. Electroconvulsive therapy was not included in this review. A systematic review was performed in MEDLINE database through PubMed, the Cochrane Collaboration’s Clinical Trials Register (CENTRAL), PsycINFO and Thomson Reuters’s Web of Science.
Results: Only 20 articles met the inclusion criteria. Randomized controlled trials demonstrated efficacy of transcranial direct current stimulation (tDCS) in five of seven trials. tDCS augmented with sertraline, fluoxetine, citalopram and escitalopram was superior to placebo and to tDCS only. A comparative trial demonstrated that the duration of tDCS sessions can modulate the effectiveness of this treatment. Open trials indicated that deep brain stimulation, epidural cortical stimulation, trigeminal nerve stimulation, magnetic seizure therapy and vagus nerve stimulation may be effective in treatment-resistant depression.
Conclusion: This review confirmed the efficacy of tDCS in MDD. Despite new evidence showing effectiveness for other non-TMS neurostimulation, their effectiveness is still unclear. Non-TMS neurostimulation RCTs with large samples and head-to-head studies comparing non-TMS neurostimulation and gold standard pharmacological treatments are still lacking.
The psychological toll of the current SARS-CoV-2 pandemic has now been widely acknowledged (Javelot et Weiner, 2020). Increased risk of post-traumatic stress disorder and obsessive-compulsive disorder has been reported in a number of studies (Javelot et Weiner, 2020). To date, however, very few studies have considered whether the current pandemic could predispose to the onset or the aggravation of panic attacks (PA) or panic disorder (PD), although the ‘panic’ word has been abundantly linked to the SARS-CoV-2 pandemic in the press (Javelot et Weiner, 2020). This is surprising given the predominance of respiratory symptoms in both COVID-19 and PD, on the one hand, and the generalized fear of contamination and fear of suffocation heightened by the pandemic, on the other hand.
Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. While there continues to be expansive research in posttraumatic stress disorder (PTSD), depression and schizophrenia, there is a relative dearth of novel medications under investigation for anxiety disorders. This review’s first aim is to summarize current pharmacological treatments (both approved and off-label) for panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and specific phobias (SP), including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), azapirones (e.g., buspirone), mixed antidepressants (e.g., mirtazapine), antipsychotics, antihistamines (e.g., hydroxyzine), alpha- and beta-adrenergic medications (e.g., propranolol, clonidine), and GABAergic medications (benzodiazepines, pregabalin, and gabapentin). Posttraumatic stress disorder and obsessive-compulsive disorder are excluded from this review. Second, we will review novel pharmacotherapeutic agents under investigation for the treatment of anxiety disorders in adults. The pathways and neurotransmitters reviewed include serotonergic agents, glutamate modulators, GABAergic medications, neuropeptides, neurosteroids, alpha- and beta-adrenergic agents, cannabinoids, and natural remedies. The outcome of the review reveals a lack of randomized double-blind placebo- controlled trials for anxiety disorders and few studies comparing novel treatments to existing anxiolytic agents. Although there are some recent randomized controlled trials for novel agents including neuropeptides, glutamatergic agents (such as ketamine and d-cycloserine), and cannabinoids (including cannabidiol) primarily in GAD or SAD, these trials have largely been negative, with only some promise for kava and PH94B (an inhaled neurosteroid). Overall, the progression of current and future psychopharmacology research in anxiety disorders suggests that there needs to be further expansion in research of these novel pathways and larger-scale studies of promising agents with positive results from smaller trials.
In this brief report we present the case of a 53 year old man with a very debilitating Generalized Anxiety Disorder successfully treated with tranylcypromine. After several failed treatment attempts following international guidelines recommendations over the course of one year and a half, tranylcypromine was prescribed which led to effective and sustained remission of anxiety symptoms for this patient. We also briefly explore treatment options for resistant cases of generalized anxiety disorder, given the major negative impacts of untreated GAD in a person’s daily functioning and quality of life.
In the recent months, the world was taken by surprise by the outbreak of a coronavirus (SARS-CoV-2) pandemic (COVID-19). The COVID-19 pandemic is a unique opportunity to advance the understanding of the association of respiratory viruses with mood disorders and suicide. In this editorial, we explore three insights to the neuropsychoneuroimmunology of mood disorders that could be taken from the COVID-19 pandemic.
Panic disorder (PD) pathophysiology is very heterogeneous, and the discrimination of distinct subtypes could be very useful. A subtype based on respiratory symptoms is known to constitute a specific subgroup. However, evidence to support the respiratory subtype (RS) as a distinct subgroup of PD with a well-defined phenotype remains controversial. Studies have focused on characterization of the RS based on symptoms and response to CO2. In this line, we described clinical and biological aspects focused on symptomatology and CO2 challenge tests in PD RS. The main symptoms that characterize RS are dyspnea (shortness of breath) and a choking sensation. Moreover, patients with the RS tended to be more responsive to CO2 challenge tests, which triggered more panic attacks in this subgroup. Future studies should focus on discriminating respiratory-related clusters and exploring psychophysiological and neuroimaging outcomes in order to provide robust evidence to confirm RS as a distinct subtype of PD.
Background: Computer simulations (CS) and virtual reality exposure are promising techniques for research and treatment of panic disorder with agoraphobia (PDA). The objective of this study was to ascertain whether a given CS was a stimulus capable of producing panic attacks (PAs), anxiety and psychophysiological changes in patients with PDA.
Methods: Thirty PDA patients and 30 healthy subjects were recruited for this study. Subjects were exposed to a 3-min CS of a situation relevant to agoraphobic patients. Anxiety, panic symptoms, PAs, heart rate, skin conductance and respiration were recorded before, during and after the CS exposure.
Results: The CS effectively induced anxiety, hyperventilation and electrodermal responses in PDA patients but not in healthy subjects. Forty percent of PDA patients had a PA while none of the control subjects had a PA. A subgroup of patients who were less sensitive to the CS than the other subgroup of PDA patients and did not present full-blown PAs still had more panic symptoms, higher anxiety levels and more respiratory irregularities than the controls.
Limitations: Low immersion and low sense of presence, lack of interaction with the environment.
Conclusions: Exposure to the CS produced effects similar to in vivo exposure, respiratory and caffeine challenges. Subsequent studies should: make direct comparisons between CS and other challenges for PDA; investigate if CS can be a tool for predicting effects of medication; determine the potential of CS as a desensitization technique for situational PAs.
Objective:
To determine whether people with a Sardinian genetic background who live in the megacities of South America have a higher frequency of hypomania than residents of Sardinia.
Methods:
A community survey of Sardinian immigrants was carried out in four Brazilian metropoles (n=218) and Buenos Aires (n=306). The results were compared with those of a study involving a similar methodology (Mood Disorder Questionnaire [MDQ] as a screening tool) conducted in seven Italian regions, including a sub-sample from Sardinia.
Results:
There was a higher prevalence of lifetime hypomania among Sardinians living in the Brazilian metropoles than among those living in Sardinia. This result was also consistent with Sardinian immigrants in Buenos Aires. After stratification by sex and age, the lifetime prevalence of MDQ scores ≥ 8 among Sardinians in South-American megacities and Sardinia was 8.6% vs. 2.9%, respectively (p < 0.0001).
Conclusions:
The higher frequency of hypomania in migrant populations appears to favor an evolutionary view in which mood disorders may be a maladaptive aspect of a genetic background with adaptive characteristics.
Introduction: Although anxiety and impulsivity are intuitively thought to be inversely correlated, increased impulsivity has been associated both with generalized anxiety disorder (GAD) diagnosis and GAD symptoms in non-clinical samples. The emotional dysregulation model of GAD posits that patients experience more frequent and intense negative emotions while having poor regulatory control over emotional states and greater negative reactivity to their emotions. We hypothesized that poor regulatory control in the presence of negative emotions might explain the increased impulsivity found in GAD patients. In this study, we examined if negative affect mediates the relationship between GAD and impulsivity.
Methods: Thirty-four GAD patients and 35 healthy controls were included, and evaluated with measurements of impulsivity, negative and positive emotions, the severity of worrying and GAD symptoms, depression, and 5-factor personality traits.
Results: Global impulsivity scores and the attentional facet of impulsivity were higher in the patient group when compared to the controls. Negative affect was correlated with global impulsivity in the patient group only and explained impulsivity in our regression model while worrying and depressive symptoms did not. An indirect relationship was found between diagnosis and impulsivity through negative affect.
Conclusion: Our study showed that the cardinal symptom of GAD – worrying – was not independently related to impulsivity in our sample. Increased impulsivity in GAD seems to be mediated by the increased presence of negative emotions, as it is common in mood and impulse-control disorders, indicating an unspecific shared vulnerability factor to psychopathology.
A master of clinical psychopharmacology, Professor Donald Franklin Klein – or Don Klein to his close admirers – was born in New York City on September 4, 1928. He grew up in the Bronx and earned a bachelor’s degree from Colby College in Maine at the age of 18, in 1947. Before being admitted to medical school, he was an undergraduate student in the biochemistry and physiology program at New York University. He earned his M.D. from the State University of New York (SUNY) Downstate in 1952. Professor Klein passed away on August 7, 2019 in Manhattan. He was married twice; first to Estelle Manette, and later to scientist and clinical psychologist Rachel Kravetz. She survives him, as do five daughters and eight grandchildren.1 Professor Klein was an overenergetic researcher in clinical psychopharmacology and psychopathology, and published in such varied areas of psychiatry as panic disorder, depression, mood disorders, childhood anxiety, schizophrenia, and in related areas of methodology and ethics. Among publications in prestigious journals such as Science, JAMA, The Lancet, The American Journal of Psychiatry and JAMA Psychiatry, Professor Klein published an update article2 and two editorials3,4 in the Brazilian Journal of Psychiatry.
Objective: To identify which clinical features and personality traits are associated with quality of life (QoL) in panic disorder (PD) patients.
Methods: This was a cross-sectional study with PD patients. The brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) and the Big Five Inventory (BFI) were used to assess QoL and personality traits respectively. The strength of correlations was measured with Pearson’s, Spearman’s, and point-biserial correlation coefficients. We also performed multiple linear regressions, considering sociodemographic data and scores from clinical scales as independent variables and QoL scores as dependent variables.
Results: A total of 98 patients were evaluated. Depressive symptoms had a strong negative correlation with QoL and, to a lesser extent, panic and anxiety symptoms were also negatively correlated with QoL. While consciousness, extraversion, and agreeableness had mild positive correlations with QoL, neuroticism had a strong negative correlation.
Conclusion: Symptoms of depression, anxiety, and panic seem to have a negative impact on the QoL of PD patients. Personality traits, especially neuroticism, may also influence QoL in these patients.
Acute administration of caffeine produces panic attacks in most Panic Disorder (PD) patients, but little is known about chronic caffeine use in these patients.
To assess caffeine use in patients with PD and to ascertain if caffeine consumption is associated with sociodemographic or clinical features.
65 adults with PD and 66 healthy controls were included in the current study. Their caffeine intake within the previous week was quantified with a questionnaire and compared. Harmful caffeine use was defined as consumption above 400 mg/day of caffeine. We tested for correlations between caffeine intake, demographic and clinical features.
Patients consumed significantly more caffeine than controls (P < 0.001). 14% (N = 9) of the PD patients made harmful use of caffeine. The use of caffeine-containing medications was observed in 40% (N = 26) of the PD patients and 6% (N = 4) of controls. Consumption of energy drinks was observed in 11% (N = 7) of PD patients and in none of the healthy subjects. Patients reported sleeping significantly less than controls (P < 0.001). In PD patients, caffeine consumption was not correlated with the presence of panic attacks or comorbidity with depression. The use of benzodiazepines or sedative medications was not correlated with caffeine intake.
High caffeine consumption in PD patients could be explained by the development of tolerance with regular use of this substance. Subtypes of sensitive and non-sensitive PD patients could also explain why some of these patients are able to tolerate high doses of caffeine.
Books and Book chapters
Citation: Freire RC, Cabrera-Abreu C, Milev R. Neurostimulation in anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder. In: Rethinking Anxiety Disorders. Yong-Ku Kim (Editor). Springer Singapore. Singapore, 2019, in press.
Citation: Freire, RC; Cirillo, PC; Nardi, AE. Clinical application of neurostimulation in depression. In: Understanding Depression: Contemporary Issues. Yong-Ku Kim (Editor). Springer Singapore. Singapore, 2018, vol. 2, pages 271-282.
Citation: Freire, RC; Nardi, AE. The effect of neurostimulation in depression. In: Understanding Depression: Contemporary Issues. Yong-Ku Kim (Editor). Springer Singapore. Singapore, 2018, vol. 1, pages 177-187.
Citation: Freire, RC; Zugliani, MM; Garcia, RF; Nardi, AE. Pharmacological and non-pharmacological approaches for treatment-resistant panic disorder. In: Panic Disorders: Assessment, Management and Research Insights. Yong-Ku Kim (Editor). NOVA Science Publishers. New York, 2018.
Citation: Nardi, Antonio Egido; Freire, Rafael Christophe R. The Panic Disorder Concept: A Historical Perspective. In: Panic Disorder: Neurobiological and Treatment Aspects. Antonio Egidio Nardi; Rafael Christophe R. Freire. (Editors). 1 ed. : Springer International Publishing, 2016, v. , p. 1-8.
Citation: Zugliani, Morena Mourao ; Freire, Rafael Christophe R. ; Nardi, Antonio Egidio. Panic Disorder Respiratory Subtype. In: Panic Disorder: Neurobiological and Treatment Aspects. Antonio Egidio Nardi; Rafael Christophe R. Freire. (Editors). 1 ed. : Springer International Publishing, 2016, v. , p. 127-138.
Citation: Hoirisch-Clapauch, Silvia ; Freire, Rafael Christophe R. ; Nardi, Antonio Egidio . Pulmonary Embolism in the Setting of Panic Attacks. In: Panic Disorder: Neurobiological and Treatment Aspects. Antonio Egidio Nardi; Rafael Christophe R. Freire. (Editors). 1 ed. : Springer International Publishing, 2016, v. , p. 211-216.
Citation: Nardi, AE ; Freire, RC . Panic Disorder: Neurobiological and Treatment Aspects. 1. ed. Cham: Springer International Publishing, 2016. v. 1.
Citation: Nardi, AE ; Freire, RC . Handbook of antidepressant medications. 1. ed. São Paulo: Casa Leitura Médica, 2011. v. 1. 56 p.
Funding and Grants
- Name: Department of Psychiatry Internal Faculty Grant (DOP-IFG)
- Funding Agency: Department of Psychiatry and Queen’s University
- Amount: $ 10,000
- Date: 2021-2022
- Name: Research Initiation Grant (RIG)
- Funding Agency: Queen’s University
- Amount: $ 30,000
- Date: 2019-2021